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Title: Continuous intravenous infusions of bromodeoxyuridine as a clinical radiosensitizer

Abstract

Twelve patients were treated with continuous intravenous (24-hour) infusions of bromodeoxyuridine (BUdR) at 650 or 1000 mg/m2/d for up to two weeks. Myelosuppression, especially thrombocytopenia, was the major systemic toxicity and limited the infusion period to nine to 14 days. However, bone marrow recovery occurred within seven to ten days, allowing for a second infusion in most patients. Local toxicity (within the radiation field) was minimal, with the exception of one of four patients, who underwent abdominal irradiation. Pharmacology studies revealed a steady-state arterial plasma level of 6 x 10(-7) mol/L and 1 x 10(-6) mol/L during infusion of 650 and 1000 mg/m2/d, respectively. In vivo BUdR uptake into normal bone marrow was evaluated in two patients by comparison of preinfusion and postinfusion in vitro radiation survival curves of marrow CFUc with enhancement ratios (D0-pre/D0-post) of 1.8 (with 650 mg/m2/d) and 2.5 (with 1000 mg/m2/d). In vivo BUdR incorporation into normal skin and tumor cells using an anti-BUdR monoclonal antibody and immunohistochemistry was demonstrated in biopsies from three patients revealing substantially less cellular incorporation into normal skin (less than 10%) compared with tumor (up to 50% to 70%). The authors conclude that local and systemic toxicity of continuous infusion ofmore » BUdR at 1000 mg/m2/d for approximately two weeks is tolerable. The observed normal tissue toxicity is comparable with previous clinical experience with intermittent (12 hours every day for two weeks) infusions of BUdR. Theoretically, a constant infusion should allow for greater incorporation of BUdR into cycling tumor cells and thus, for further enhancement of radiosensitization.« less

Authors:
; ; ; ; ; ; ;
Publication Date:
Research Org.:
National Cancer Inst., Bethesda, MD
OSTI Identifier:
5615268
Resource Type:
Journal Article
Journal Name:
J. Clin. Oncol.; (United States)
Additional Journal Information:
Journal Volume: 2:10
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; URIDINE; RADIOSENSITIVITY EFFECTS; TOXICITY; BONE MARROW; CFU; INTRAVENOUS INJECTION; MONOCLONAL ANTIBODIES; NEOPLASMS; PATIENTS; RADIOTHERAPY; SKIN; SURVIVAL CURVES; TUMOR CELLS; ANIMAL CELLS; ANIMAL TISSUES; ANTIBODIES; AZINES; BODY; DISEASES; HEMATOPOIETIC SYSTEM; HETEROCYCLIC COMPOUNDS; HYDROXY COMPOUNDS; INJECTION; INTAKE; MEDICINE; NUCLEAR MEDICINE; NUCLEOSIDES; NUCLEOTIDES; ORGANIC COMPOUNDS; ORGANIC NITROGEN COMPOUNDS; ORGANS; PYRIMIDINES; RADIOLOGY; RIBOSIDES; THERAPY; TISSUES; URACILS; 550603* - Medicine- External Radiation in Therapy- (1980-)

Citation Formats

Kinsella, T J, Mitchell, J B, Russo, A, Aiken, M, Morstyn, G, Hsu, S M, Rowland, J, and Glatstein, E. Continuous intravenous infusions of bromodeoxyuridine as a clinical radiosensitizer. United States: N. p., 1984. Web.
Kinsella, T J, Mitchell, J B, Russo, A, Aiken, M, Morstyn, G, Hsu, S M, Rowland, J, & Glatstein, E. Continuous intravenous infusions of bromodeoxyuridine as a clinical radiosensitizer. United States.
Kinsella, T J, Mitchell, J B, Russo, A, Aiken, M, Morstyn, G, Hsu, S M, Rowland, J, and Glatstein, E. 1984. "Continuous intravenous infusions of bromodeoxyuridine as a clinical radiosensitizer". United States.
@article{osti_5615268,
title = {Continuous intravenous infusions of bromodeoxyuridine as a clinical radiosensitizer},
author = {Kinsella, T J and Mitchell, J B and Russo, A and Aiken, M and Morstyn, G and Hsu, S M and Rowland, J and Glatstein, E},
abstractNote = {Twelve patients were treated with continuous intravenous (24-hour) infusions of bromodeoxyuridine (BUdR) at 650 or 1000 mg/m2/d for up to two weeks. Myelosuppression, especially thrombocytopenia, was the major systemic toxicity and limited the infusion period to nine to 14 days. However, bone marrow recovery occurred within seven to ten days, allowing for a second infusion in most patients. Local toxicity (within the radiation field) was minimal, with the exception of one of four patients, who underwent abdominal irradiation. Pharmacology studies revealed a steady-state arterial plasma level of 6 x 10(-7) mol/L and 1 x 10(-6) mol/L during infusion of 650 and 1000 mg/m2/d, respectively. In vivo BUdR uptake into normal bone marrow was evaluated in two patients by comparison of preinfusion and postinfusion in vitro radiation survival curves of marrow CFUc with enhancement ratios (D0-pre/D0-post) of 1.8 (with 650 mg/m2/d) and 2.5 (with 1000 mg/m2/d). In vivo BUdR incorporation into normal skin and tumor cells using an anti-BUdR monoclonal antibody and immunohistochemistry was demonstrated in biopsies from three patients revealing substantially less cellular incorporation into normal skin (less than 10%) compared with tumor (up to 50% to 70%). The authors conclude that local and systemic toxicity of continuous infusion of BUdR at 1000 mg/m2/d for approximately two weeks is tolerable. The observed normal tissue toxicity is comparable with previous clinical experience with intermittent (12 hours every day for two weeks) infusions of BUdR. Theoretically, a constant infusion should allow for greater incorporation of BUdR into cycling tumor cells and thus, for further enhancement of radiosensitization.},
doi = {},
url = {https://www.osti.gov/biblio/5615268}, journal = {J. Clin. Oncol.; (United States)},
number = ,
volume = 2:10,
place = {United States},
year = {Mon Oct 01 00:00:00 EDT 1984},
month = {Mon Oct 01 00:00:00 EDT 1984}
}